Drugs or pharmaceutical and medicinals which are amines or have an amine function therein undergo protonation at physiological pH and are not always transported optimally through biological membranes in the body. No bioreversible chemical modification of the amine-type drugs, or pharmaceutical and medicinals having amine functions thereon to prevent protonation are known. Enamines have been studied in the past, but they depend on acid catalyzed hydrolysis for regeneration, not on an enzymatic process, and thus are unsatisfactory. Also, carbamate ester latentiation of physiologically active amines has been described in A. J. Verbiscar and L. G. Agood, Journal of Medicinal Chemistry, 13, 1176 (1970), but these compounds were also not bioreversible.
For the purposes of this specification, the term "prodrug" denotes a derivative of a known and proven primary or secondary amino functional drug (e.g. timolol, methyldopa, thiabendazole, etc.) which derivative, when administered to a warm-blooded animal, "cleaves" in such a manner as to release the proven drug form at its target site or sites of activity. The enzymatic and/or chemical hydrolytic "cleavage" of the compounds of the instant invention occurs in a manner such that the proven drug form is released while the remaining "cleaved" moiety remains nontoxic and is metabolized in such a manner that nontoxic, metabolic products are produced.